X-54440800-C-A

Variant names:

• chrX-54440800-C-A
• NM_058163.3:c.172+20C>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001346790.2(TSR2):​c.-196C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000394 in 1,014,138 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000039 (0 hom. 0 hem.)
• Consequence: TSR2 NM_001346790.2 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.297
• Publications: 0 publications found

Genes affected

TSR2 (HGNC:25455): (TSR2 ribosome maturation factor) The protein encoded by this gene appears to repress the transcription of NF-kappaB and may be involved in apoptosis. Defects in this gene are a cause of Diamond-Blackfan anemia. [provided by RefSeq, Oct 2016]

TSR2 Gene-Disease associations (from GenCC):

• Diamond-Blackfan anemia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Diamond-Blackfan anemia 14 with mandibulofacial dysostosis

  Inheritance: XL Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant X-54440800-C-A is Benign according to our data. Variant chrX-54440800-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1974498.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001346790.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSR2	NM_058163.3	MANE Select	c.172+20C>A		intron	N/A	NP_477511.1	Q969E8
	TSR2	NM_001346790.2		c.-196C>A		5_prime_UTR	Exon 2 of 5	NP_001333719.1
	TSR2	NM_001346791.2		c.-205C>A		5_prime_UTR	Exon 2 of 5	NP_001333720.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSR2	ENST00000375151.5	TSL:1 MANE Select	c.172+20C>A		intron	N/A	ENSP00000364293.4	Q969E8
	TSR2	ENST00000908048.1		c.172+20C>A		intron	N/A	ENSP00000578107.1
	TSR2	ENST00000960847.1		c.172+20C>A		intron	N/A	ENSP00000630906.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000394 AC: 4 AN: 1014138 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 299432

African (AFR) AF: 0.00 AC: 0 AN: 24520

American (AMR) AF: 0.000135 AC: 4 AN: 29591

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16196

East Asian (EAS) AF: 0.00 AC: 0 AN: 28228

South Asian (SAS) AF: 0.00 AC: 0 AN: 45646

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37950

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3737

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 785455

Other (OTH) AF: 0.00 AC: 0 AN: 42815

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	5.1
DANN	Benign	0.75
PhyloP100		0.30
PromoterAI		-0.11	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chrX-54467233;